ArticleCell reports2017
Genome-Scale Architecture of Small Molecule Regulatory Networks and the Fundamental Trade-Off between Regulation and Enzymatic Activity.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Model-based inference of enzyme inhibitions from perturbation-induced metabolic dynamics.bioRxiv : the preprint server for biology · 2026Article
- The return of metabolism: biochemistry and physiology of glycolysis.Biological reviews of the Cambridge Philosophical Society · 2026Review
- Microbial Metabolism: Primary and Secondary Metabolites.Progress in molecular and subcellular biology · 2026Review
- Redox poise in R. rubrum phototrophic growth drives large-scale changes in macromolecular pathways.PLoS computational biology · 2025Article
- Systematic identification of allosteric effectors inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Time and dose selective glucose metabolism for glucose homeostasis and energy conversion in the liver.NPJ systems biology and applications · 2024Article
- Quantitative principles of microbial metabolism shared across scales.Nature microbiology · 2024Review
- Local flux coordination and global gene expression regulation in metabolic modeling.Nature communications · 2023Article
- Transcriptome-guided metabolic network analysis reveals rearrangements of carbon flux distribution inmSystems · 2023Article
- Principles of metabolome conservation in animals.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insight into de-regulation of amino acid feedback inhibition: a focus on structure analysis method.Microbial cell factories · 2023Review
- A Reduction of Transcriptional Regulation in Aquatic Oligotrophic Microorganisms Enhances Fitness in Nutrient-Poor Environments.Microbiology and molecular biology reviews : MMBR · 2023Review
- Yeast increases glycolytic flux to support higher growth rates accompanied by decreased metabolite regulation and lower protein phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Toward mechanistic modeling and rational engineering of plant respiration.Plant physiology · 2023Article
- Control Analysis of Cooperativity and Complementarity in Metabolic Regulations: The Case of NADPH Homeostasis.Metabolites · 2023Article
- The Knowns and Unknowns in Protein-Metabolite Interactions.International journal of molecular sciences · 2023Review
- Prediction of metabolite-protein interactions based on integration of machine learning and constraint-based modeling.Bioinformatics advances · 2023Article
- Protein-Metabolite Interactions Shape Cellular Metabolism and Physiology.Methods in molecular biology (Clifton, N.J.) · 2023Article
- An approach to learn regulation to maximize growth and entropy production rates in metabolism.Frontiers in systems biology · 2023Article
- Characterization of an Entner-Doudoroff pathway-activated Escherichia coli.Biotechnology for biofuels and bioproducts · 2022Article
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Metabolic flux is in part regulated by endogenous small molecules that modulate the catalytic activity of an enzyme, e.g., allosteric inhibition. In contrast to transcriptional regulation of enzymes, technical limitations have hindered the production of a genome-scale atlas of small molecule-enzyme regulatory interactions. Here, we develop a framework leveraging the vast, but fragmented, biochemical literature to reconstruct and analyze the small molecule regulatory network (SMRN) of the model organism Escherichia coli, including the primary metabolite regulators and enzyme targets. Using metabolic control analysis, we prove a fundamental trade-off between regulation and enzymatic activity, and we combine it with metabolomic measurements and the SMRN to make inferences on the sensitivity of enzymes to their regulators. Generalizing the analysis to other organisms, we identify highly conserved regulatory interactions across evolutionarily divergent species, further emphasizing a critical role for small molecule interactions in the maintenance of metabolic homeostasis.
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